A Wearable Patch To Monitor Estrogen

The sex hormone commonly known as estrogen plays an important role in women’s health and fertility.

By Emily Velasco, Caltech

High levels of estrogen in the body are associated with breast and ovarian cancers, while low levels of estradiol can result in osteoporosis, heart disease, and even depression. (Estrogen is a class of hormones that includes estradiol as the most potent form). Estradiol is also necessary for the development of secondary sexual characteristics in women and regulates the reproductive cycle.

The hormone estradiol is often monitored at a clinic, but this usually requires the patient to , have blood drawn for analysis in a lab. Even at-home testing kits require that samples of blood or urine to be mailed to a lab.

But now Caltech researchers have developed a wearable sensor that monitors estradiol by detecting its presence in sweat. The researchers say the sensor may one day make it easier for women to monitor their estradiol levels at home and in real time.

The research was conducted in the lab of Wei Gao, assistant professor of medical engineering, investigator with the Heritage Medical Research Institute, and Ronald and JoAnne Willens Scholar. In recent years, Gao has developed sweat sensors that detect cortisol, a hormone associated with stress; the presence of the COVID-19 virus; a biomarker indicating inflammation in the body; and a whole slew of other nutrients and biological compounds.

“People often asked me if I could make the same kind of sweat sensor for female hormones, because we know how much those hormones impact women’s health,” Gao says.

Women who would benefit from estradiol monitoring include those who are attempting to conceive a child, either naturally or through in vitro fertilization. “Estrogen increases before ovulation,” he says. “With this sweat sensor, we would be able to give people notice ahead of time.”

Other individuals who could benefit from a wearable estrogen sensor are those undergoing hormone replacement therapy (HRT) because their bodies do not produce sufficient estradiol. In these patients, estradiol levels need to be carefully monitored to ensure they are taking the correct dosage.

The sensor Gao’s team is built on a flexible plastic membrane; has tiny etched passages (microfluidics) for channeling small amounts of sweat into the sensor; and inkjet-printed gold nanoparticles and titanium carbide films (known as MXenes) that give the sensor a large surface area and electrical conductivity to increase its sensitivity.

The primary challenge, and what dictated changes in the sensor’s design this time around, is that estradiol, which already is present at fairly low levels in the blood, is roughly 50 times less concentrated in sweat.

In the new sensor, when an aptamer binds to an estradiol molecule, it releases a redox molecule. That molecule is recaptured by a nearby electrode made of MXene-coated gold nanoparticles, generating an electrical signal. That data is wirelessly transmitted to an app that runs on a smart phone, providing a simple interface for the user.  Testing in the laboratory has shown that the sensor can reliably and accurately track the changing levels of estradiol in sweat over the course of the reproductive cycle.

Gao says he plans to continue working on this technology to allow it to monitor other female hormones. He also hopes to miniaturize all these sensors so they could all fit inside an inconspicuous ring that could be worn on the finger.

The paper describing the research, “A wearable aptamer nanobiosensor for non-invasive female hormone monitoring,” appeared in the Sept. 28 issue of Nature Nanotechnology. Co-authors are postdoctoral scholar research associates in medical engineering Cui Ye, Minqiang Wang, and Juliane R. Sempionatto; medical engineering graduate students Jihong Min (MS ’19), Heather Lukas (MS ’21), Jiahong Li (MS ’23), and Changhao Xu (MS ’20); and Roland Yingjie Tay, formerly of Caltech and now with Nanyang Technological University of Singapore.

Funding for the research was provided by the National Institutes of Health, the National Science Foundation, the Office of Naval Research, an American Cancer Society Research Scholar Grant, and a Sloan Research Fellowship.

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